Long non‑coding RNA HOTTIP enhances the fibrosis of lung tissues by regulating the miR‑744‑5p/PTBP1 signaling axis

Abstract

Fibrosis of lung tissue can induce the occurrence and development of numerous types of lung disease. The expression levels of the long non-coding RNA (lncRNA) HOXA distal transcript antisense RNA (HOTTIP) have been reported to be upregulated during the development of fibrosis in liver tissues, which subsequently activated hepatic stellate cells. However, whether the lncRNA HOTTIP participates in the occurrence and development of lung fibrosis remains unknown. The present study aimed to investigate the role of lncRNA HOTTIP in lung fibrosis and its potential mechanism. In the present study, A549 cells were stimulated with TGF-β1 to induce lung fibrosis in vitro. A549 was transfected with short hairpin RNA-HOTTP, overexpression-polypyrimidine tract binding protein 1 (PTBP1), microRNA (miR)-744-5p mimic or miR-744-5p to regulate gene expression. Cell proliferation and migration were determined using 5'-ethynl-2'-deoxyuridine and wound healing assays, respectively. The expression levels of α-smooth muscle actin, collagen I, collagen III and fibronectin 1 were analyzed using western blotting. starBase was used to identify molecules that may interact with the lncRNA HOTTIP and dual luciferase reporter assays were used to validate the findings. Moreover, an in vivo lung fibrosis model was established by bleomycin induction in mice. Histological injury was observed using hematoxylin and eosin and masson staining. The results of the present study revealed that the proliferation and migration of A549 cells were both suppressed following the knockdown of HOTTIP. The lncRNA HOTTIP was found to target and downregulate the expression levels of miR-744-5p. The overexpression of miR-744-5p inhibited the proliferation and migration of A549 cells. Furthermore, miR-744-5p targeted and downregulated the expression levels of PTBP1. It was subsequently demonstrated that the overexpression of PTBP1 rescued miR-744-5p-induced suppression of the proliferation and migration of A549 cells. The knockdown of lncRNA HOTTIP expression also relieved the fibrosis of the lung tissues of mice. In conclusion, the results of the present study suggested that the lncRNA HOTTIP may promote the fibrosis of lung tissues by downregulating the expression levels of miR-744-5p and upregulating the expression levels of PTBP1.

LncRNA HOTTIP promotes LPS‐induced lung epithelial cell injury by recruiting DNMT1 to epigenetically regulate SP‐C

“…Previous studies have shown that HOTTIP was upregulated in fibrotic lung tissues and was related to cell proliferation and migration. 23 Moreover, HOTTIP was upregulated in lung cancer tissues and promoted the tumor progression, 24 suggesting that HOTTIP is crucial in maintaining lung homeostasis and that its dysregulation may contribute to the development of lung disease even lung cancer. Nevertheless, the function of HOTTIP in ALI remains unknown.…”

LncRNA HOTTIP as a diagnostic biomarker for acute respiratory distress syndrome in patients with sepsis and to predict the short-term clinical outcome: a case-control study

“…And pulmonary fibrosis is a major cause of poor prognosis in ARDS in patients with sepsis [ 2 ]. Importantly, HOTTIP was noticeably upregulated in patients with pulmonary fibrosis and enhanced lung tissue fibrosis via miR-744-5p/PTBP1 [ 10 ].…”

“…In particular, ARDS is characterized by a rapid fibroproliferative response in addition to early inflammation. Pulmonary fibrosis is believed to be the main cause of a poor prognosis in patients with ARDS due to sepsis [ 2 ], while Li et al in 2021 found that silencing HOTTIP alleviated pulmonary fibrosis [ 10 ]. Furthermore, elevated HOTTP was also observed in patients with sepsis and was associated with their cardiac dysfunction.…”

Polypyrimidine tract binding protein 1 exacerbates cardiac fibrosis by regulating fatty acid‐binding protein 5

“… 5 In addition, up‐regulation of PTBP1 by lncRNA HOTTIP accelerated the progression of pulmonary fibrosis. 17 Although the contribution of PTBP1 to doxorubicin‐induced cardiomyocyte fibrosis has been documented, 7 the modulation of PTBP1 in CF proliferation and deposition of collagen protein remains unclear. Our results for the first time revealed that PTBP1 facilitated the proliferation and collagen protein expression of CFs, providing novel evidence for PTBP1 as a contributor to cardiac fibrosis.…”

“…reported that PTBP1 was involved in the regulation of pyroptosis and M1 macrophage polarization, which affected liver fibrosis 5 . In addition, up‐regulation of PTBP1 by lncRNA HOTTIP accelerated the progression of pulmonary fibrosis 17 . Although the contribution of PTBP1 to doxorubicin‐induced cardiomyocyte fibrosis has been documented, 7 the modulation of PTBP1 in CF proliferation and deposition of collagen protein remains unclear.…”